We developed a new method -- "fracture-permeation" -- to assess the compactness of the cytoplasmic matrix. Cells fixed in glutaraldehyde were frozen, cross-fractured in liquid nitrogen and thawed. Cell fragments were immersed in concentrated solutions of native ferritin (30% w/v). Permeation by ferritin, and electron-dense probe, tested the existence and distribution of intermolecular spaces within the cytoplasmic matrix of glutaraldehyde-fixed cells. Ferritin molecules were unable to permeate the cross-linked cytoplasm of human neutrophils, fungal zoospores and cysts, used here as examples of non-dividing cells with low levels of protein synthesis. In resting lymphocytes from human peripheral blood permeation of ferritin was lilmited or absent, but it became massive in cells activated by phytohaemagglutin. Massive permeation of ferritin was also observed within the cytoplasmic matrix of active cells (sarcoplasm of skeletal muscle, fungal sporangia, germinating cysts). We show that compactness of the cytoplasmic matrix depends on the physiological state of the cell: in cross-fractured skeletal muscle ferritin permeation of the sarcomere readily differentiates rigor from relaxed states. Our results accord with the existence in the native cytoplasm of interactive soluble and insoluble protein phases.